Expression of the protooncogene bcl-2 in Alzheimer's disease brain

O’Barr, Stephen A.; Schultz, James J.; Rogers, Joseph

doi:10.1016/0197-4580(95)02024-1

Cited by 49 publications

(22 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Specific expression only in microglia may explain the reduced resistance of neurons to injury in the aged brain. A similar result is observed for Bcl-2, in which a three fold increase of Bcl-2 protein occurs in AD brain in comparison to control adult brain (125). In AD brain Bcl-2 protein is predominantly localized to activated astrocytes, not neurons.…”

Section: Developmentally Regulated Genessupporting

confidence: 69%

Alzheimer s disease and brain development common molecular pathways

Jordan‐Sciutto

Bowser²

1998

Front Biosci

View full text Add to dashboard Cite

Research on the causes and treatments of Alzheimer's disease (AD) has led investigators down numerous avenues. Although many models have been proposed, no single model of AD satisfactorily accounts for all neuropathologic findings as well as the requirement of aging for disease onset. The mechanisms of disease progression are equally unclear. We hypothesize that alternative gene expression during AD plays a critical role in disease progression. Numerous developmentally regulated genes and cell cycle proteins have been shown to be re-expressed or activated during AD. These proteins include transcription factors, members of the cell cycle regulatory machinery, and programmed cell death genes. Such proteins play an important role during brain development and would likely exert powerful effects if re-expressed in the adult brain. We propose that the re-expression or activation of developmentally regulated genes define molecular mechanisms active both during brain development and in AD

show abstract

Section: Developmentally Regulated Genessupporting

confidence: 69%

Alzheimer s disease and brain development common molecular pathways

Jordan‐Sciutto

Bowser²

1998

Front Biosci

View full text Add to dashboard Cite

show abstract

“…Subsequent studies confirmed the glial localization of increased Bcl-2 in AD. O'Barr et al (1996) saw 3 fold increases in Bcl-2 in AD brain by immunoblot, which they attributed primarily due to changes in astrocytes (from immunocytochemical analyses). Tortosa et al (1998) reported no increase in neuronal Bcl-2, nor any differences between neurons with or without neurofibrillary pathology, but did note an increased Bcl-2 staining in reactive glial cells near plaques.…”

Section: Discussionmentioning

confidence: 99%

Up-regulation of Bcl-2 in APP transgenic mice is associated with neuroprotection

Karlnoski

Wilcock

Dickey

et al. 2007

Neurobiology of Disease

View full text Add to dashboard Cite

Aβ-induced neurodegeneration is limited in APP and APP+PS1 transgenic mice. In middle-aged APP+PS1 transgenic mice, we found significantly increased Bcl-2 expression. The increase in Bcl-2 is restricted to amyloid-containing brain regions and is not found at young ages, suggesting that Aβ deposition is the stimulus for increased Bcl-2. Western blot results were confirmed with immunohistochemistry, and qRT-PCR. In addition, we found that APP transgenic mice were protected from neurotoxicity caused by an injection of bak BH3 fusion peptides, known to induce apoptosis by antagonizing bcl protein activity. Nissl and fluorojade stained slides showed that the active bak BH3 peptide caused substantial neuronal loss in the dentate gyrus and CA3 regions of nontransgenic, but not APP mice. The inactive mutant bak BH3 peptide did not cause degeneration in any mice. These data demonstrate that the increased Bcl-2 expression in brain regions containing Aβ deposits is associated with neuroprotection. KeywordsBax; APP+PS1 transgenic mice; Alzheimer's disease; neurotoxicity; Aβ; apoptosis The amyloid cascade hypothesis states that the dysregulation of amyloid precursor protein (APP) processing and Aβ production are the major causes for neuronal death and dysfunction leading to dementia in Alzheimer's disease (Hardy and Selkoe, 2002). Genetic and environmental factors, such as APP or PS-1 mutations, cause an accumulation of Aβ which forms diffuse and compact plaques. These plaques are thought to cause oxidative stress, activate microglia and astrocytes, causing cytokine release, inflammation and altered ionic homeostasis, culminating in cytotoxicity and neuronal death.The Aβ peptide can directly induce neuronal apoptosis in vitro (Pike et al., 1993); (Hensley et al., 1995); (Schubert and Chevion, 1995); (Wogulis et al., 2005). Intracellular Aβ may activate apoptosis by interacting with the endoplasmic reticulum and endosomes and by binding to alcohol dehydrogenase within the mitochondria (Dickson, 2004). Aβ also induces changes in nitric oxide production and mitochondrial activity facilitating apoptosis (Keil et al., 2004). InCorresponding author: Dave Morgan, Alzheimer Research Laboratory, University of South Florida 12901 Bruce B. Downs Blvd MDC Box 9 Tampa, FL 33612, Scientist.dave@gmail.com Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Aβ-induced neuronal toxicity is limited in the APP transgenic mouse models of AD. A modest reduction in hippocampal neurons was found in old APP23 mice, but the cortical neuron census was unaffected despite extensive amyloid deposition (Calhou...

show abstract

“…Oxidative stress was documented in AD brains (138,160,170,172,199,245,246) and it was postulated that mitochondria, a well-recognized source of reactive oxygen species (ROS) production (39), could be responsible (11,264). Mitochondria were discovered to play a central role in programmed cell death (115,148,216,301), a process felt possibly to mediate neuron loss in AD (57,65,66,151,194,222,231,244,251). Age-dependent increases in mtDNA damage, either in the form of oxidative modifications or frank mutations, were documented (54,179).…”

Section: Mitochondria Are Increasingly Implicated In Ad and Ad Modelsmentioning

confidence: 99%